The analysis of a substance to determine its composition may be necessary for many applications, including toxicology, forensics and environmental testing, as well as food and drug research. Often, samples to be analyzed are analyzed for the presence of numerous different analytes of interest. Such samples may, for example, be in the form of bodily fluids taken from test subjects, which fluids often include both drug metabolites of interest, as well as irrelevant endogenous ions from the test subject. Within complex samples, correctly determining the presence or absence as well as the quantities of a large number of analytes of interest, can be difficult and time-consuming.
Mass spectrometers are often used for producing a mass spectrum of a sample to find its composition. This is normally achieved by ionizing the sample and separating ions of differing masses and recording their relative abundance by measuring intensities of ion flux. For example, with time-of-flight mass spectrometers, ions are pulsed to travel a predetermined flight path. The ions are then subsequently recorded by a detector. The amount of time that the ions take to reach the detector, the “time-of-flight”, may be used to calculate the ion's mass to charge ratio, m/z.
Additional information (in addition to an ion's precursor mass) can then be obtained by fragmenting the ion via CID (collision induced dissociation) in a collision cell (or other means) to generate an MSMS spectrum. In most instruments with MSMS capabilities, the process of generating a mass spectrum, selecting a precursor ion and generating an MSMS (mass spectrum/mass spectrum) spectrum can be performed in an automated mode. This mode of acquisition is frequently referred to as Information Dependant Acquisition (IDA) or Data Dependant Experiment (DDE).
Chromatographic equipment such as a liquid chromatograph may be used to elute or release ions from a sample into the mass spectrometer over a period of time. Multiple reaction monitoring (MRM) or other techniques may be used to analyze the ions received by the mass spectrometer.
For complex samples, LC/MS quantitiation techniques using MRM frequently involve interfering matrix components exhibiting the same Q1 and Q3 masses as the analytes of interest. As a result, it may be difficult to determine which peak in a chromatogram represents the particular analyte of interest. There may also be small changes in retention time that increase the difficulty of peak finding. When dealing with a small number of analytes, this problem can usually be addressed by using specific sample cleanup techniques, isotopically enriched versions of the analytes as internal standards, or even sufficient manual intervention. For large numbers of analytes, however, such solutions are impractical.
The applicants have accordingly recognized a need for systems and methods for analyzing and identifying ions from samples.